Polyphenols, including tannins, are phytochemicals with pronounced antimicrobial properties. We studied the activity of two hydrolysable tannins, (i) gallotannin—1,2,3,4,5-penta-O-galloyl-β-D-glucose (PGG) and (ii) ellagitannin—1,2-di-O-galloyl-4,6-valoneoyl-β-D-glucose (dGVG), applied alone and in combination with antibiotics against Staphylococcus aureus strain 8324-4. We also evaluated the effect of these tannins on bacterial membrane integrity and fluidity and studied their interaction with membrane proteins and lipids. A correlation between the antimicrobial activity of the tannins and their membranotropic action depending on the tannin molecular structure has been demonstrated. We found that the antibacterial activity of PGG was stronger than dGVG, which can be associated with its larger flexibility, dipole moment, and hydrophobicity. In addition, we also noted the membrane effects of the tannins observed as an increase in the size of released bacterial membrane vesicles.

Mutations in many visual cycle enzymes in photoreceptors and retinal pigment epithelium (RPE) cells can lead to the chronic accumulation of toxic retinoid byproducts, which poison photoreceptors and the underlying RPE if left unchecked. Without a functional ATP-binding cassette, sub-family A, member 4 (ABCA4), there is an elevation of all- trans -retinal and prolonged buildup of all- trans -retinal adducts, resulting in a retinal degenerative disease known as Stargardt-1 disease. Even in this monogenic disorder, there is significant heterogeneity in the time to onset of symptoms among patients. Using a combination of molecular techniques, we studied Abca4 knockout (simulating human noncoding disease variants) and Abca4 knock-in mice (simulating human misfolded, catalytically inactive protein variants), which serve as models for Stargardt-1 disease. We compared the two strains to ascertain whether they exhibit differential responses to agents that affect cytokine signaling and/or ceramide metabolism, as alterations in either of these pathways can exacerbate retinal degenerative phenotypes. We found different degrees of responsiveness to maraviroc, a known immunomodulatory CCR5 antagonist, and to the ceramide-lowering agent AdipoRon, an agonist of the ADIPOR1 and ADIPOR2 receptors. The two strains also display different degrees of transcriptional deviation from matched WT controls. Our phenotypic comparison of the two distinct Abca4 mutant-mouse models sheds light on potential therapeutic avenues previously unexplored in the treatment of Stargardt disease and provides a surrogate assay for assessing the effectiveness for genome editing.

Neisseria gonorrhoeae is an etiological agent of gonorrhea, which remains a global health problem. This bacterium possesses MutL and MutS DNA repair proteins encoded by mutL and mutS genes, whose inactivation causes a mutator phenotype. We have demonstrated the differential gene expression in N. gonorrhoeae mutL and mutS mutants using DNA microarrays. A subset of differentially expressed genes encodes proteins that can influence adhesion and biofilm formation. Compared to the wild-type strain, N. gonorrhoeae mutL and mutS mutants formed denser biofilms with increased biofilm-associated biomass on the abiotic surface. The N. gonorrhoeae mutS::km, but not the mutL mutant, was also more adherent and invasive to human epithelial cells. Further, during infection of epithelial cells with N. gonorrhoeae mutS::km, the expression of some bacterial genes encoding proteins that can influence gonococcal adhesion was changed compared with their expression in cells infected with the wild-type gonococcus, as well as of human genes’ encoding receptors utilized by N. gonorrhoeae (CD46, CEACAM 1, HSPG 2). Thus, deficiency in the mutS gene resulting in increased mutation frequency in singular organisms can be beneficial in populations because these mutants can be a source of features linked to microbial fitness.

Bacteria of the Neisseria genus are Gram-negative diplococci including both pathogenic and commensal species. We focused on pathogenic Neisseria gonorrhoeae and commensal Neisseria sicca. We have demonstrated that not only N. gonorrhoeae, but also N. sicca induce the secretion of pro-inflammatory cytokines IL-6, TNF-α, and chemokines CXCL8 and CCL20 by infected epithelial cells. However, N. sicca triggers a lesser effect than does N. gonorrhoeae. Furthermore, N. gonorrhoeae and N. sicca invoke distinct effects on the expression of genes (JUNB, FOSB, NFKB1, NFKBIA) encoding protein components of AP-1 and NF-κB transcription factors. We have also shown that the infection of epithelial cells by N. gonorrhoeae leads to significant overexpression of the long non-coding RNAs (lncRNAs), including MALAT1, ERICD, and RP11-510N19.5. This effect was not identified for N. sicca. In conclusion, data on the expression of lncRNAs and cytokine secretion in response to Neisseria spp. exposure indicate new directions for research on Neisseria-host interactions and can provide further insights into virulence of not only pathogenic, but also commensal Neisseria spp.

Neisseria gonorrhoeae (gonococcus) is a Gram-negative bacteria and an etiological agent of the sexually transmitted disease – gonorrhea. N. gonorrhoeae possesses many mechanism to evade the innate immune response of the human host. Most are related to serum resistance and avoidance of complement killing. However the clinical symptoms of gonorrhea are correlated with a significant presence of neutrophils, whose response is also insufficient and modulated by gonococci. 1. Introduction. 2. Adherence ability. 3. Serum resistance and complement system. 4. Neutrophils. 4.1. Phagocytosis. 4.1.1. Oxygen-dependent intracellular killing. 4.1.2. Oxygen-independent intracellular killing. 4.2. Neutrophil extracellular traps. 4.3. Degranulation. 4.4. Apoptosis. 5. Summary

Existence of moonlighting proteins in microorganisms is a known phenomenon, yet still not well understood. Moonlighting proteins have at least two independent biological functions, which must be performed by one polypeptide chain without separation into protein domains. Most of these proteins, beside their role in the cytoplasm, play an important role outside of the cell i.e. they take part in the process of pathogenesis by binding and activating host’s plasminogen. The existence of moonlighting proteins complicates the understanding of pathogenicity and virulence of many common bacteria as well as their role in commensal bacteria. Many of moonlighting proteins occurring in commensal bacteria appear to perform similar functions to proteins discovered in pathogenic bacteria, e.g. binding extracellular matrix. Moonlighting proteins found in bacteria are mostly housekeeping enzymes, especially from the glycolytic pathway, such as enolase, aldolase, dehydrogenase as well as heat-shock proteins and transcriptional factors. 1. Introduction. 2. Involvement of moonlighting proteins in bacterial pathogenesis. 3. Effect of moonlighting proteins on the immune system. 4. Moonlighting proteins in lactic acid bacteria.5. Transportation of moonlighting proteins to the bacterial surface. 6. Evolution of moonlighting proteins. 7. Detection of moonlighting proteins. 8. Summary 1. Wprowadzenie. 2. Udział białek wielofunkcyjnych w bakteryjnej patogenezie. 3. Wpływ białek wielofunkcyjnych na układ odpornościowy. 4. Obecność białek wielofunkcyjnych u bakterii kwasu mlekowego. 5. Transport białek wielofunkcyjnych na powierzchnię komórek bakteryjnych. 6. Ewolucja białek wielofunkcyjnych. 7. Wykrywanie białek wielofunkcyjnych. 8. Podsumowanie